title: Antiparasitic and antimicrobial indolizidines from the leaves of Prosopis glandulosa var. glandulosa.
abstract: A new indolizidine alkaloid, named Δ¹,⁶-juliprosopine (1), together with previously known indolizidine analogs (2- 6), was isolated from the leaves of Prosopis glandulosa var. glandulosa, collected from Nevada, USA; while two other known indolizidines, juliprosopine (6) and juliprosine (7), were isolated from P. glandulosa leaves collected in Texas, USA. The structures of compound 1 and 7 were determined using a combination of NMR and MS techniques. Compound 7 exhibited potent antiplasmodial activity against Plasmodium falciparum D6 and W2 strains with IC (50) values of 170 and 150 ng/mL, respectively, while 1 was found to be less active (IC₅₀ values 560 and 600 ng/mL, respectively). Both compounds were devoid of VERO cells toxicity up to a concentration of 23 800 ng/mL. The antileishmanial activity of indolizidines was evaluated against Leishmania donovani promastigotes, axenic amastigotes, and amastigotes in THP1 macrophage cultures. When tested against macrophage cultures, the tertiary bases (1, 3, 6) were found to be more potent than quaternary salts (2, 5, 7), displaying IC₅₀ values between 0.8-1.7 µg/mL and 3.1-6.0 µg/mL, respectively. In addition, compound 7 showed potent antifungal activity against Cryptococcus neoformans and antibacterial activity against Mycobacterium intracellulare, while 1 was potent only against C. neoformans and weakly active against other organisms.
authors.affiliation: National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Aziz Abdur
authors.initials: AA
authors.lastname: Rahman
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Samoylenko
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Jacob
authors.forename: Rajnish
authors.initials: R
authors.lastname: Sahu
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Jain
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Ilias
authors.initials: I
authors.lastname: Muhammad
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003455:Cryptococcus neoformans / Q000187:drug effects; D006801:Humans; D054836:Indolizidines / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D015394:Molecular Structure; D015269:Mycobacterium avium Complex / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal; D010963:Plasmodium falciparum / Q000187:drug effects; D029862:Prosopis / Q000737:chemistry*; D013781:Texas
chemical_list: D000470:Alkaloids; D000890:Anti-Infective Agents; D054836:Indolizidines; D010936:Plant Extracts